ORCID Profile
0000-0002-6224-1286
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Biologically active molecules | Pharmacology and pharmaceutical sciences | Basic pharmacology |
Publisher: Elsevier BV
Date: 10-2013
DOI: 10.1016/J.BMC.2013.07.045
Abstract: Several libraries of similarly N-substituted 8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes (9), N-methyl-8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes (14), and N-methyl-11-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecan-8-ones (13) were synthesised and screened against a panel of CNS targets in order to develop structure-affinity relationships for cage-modified trishomocubane σ receptor ligands based on the N-substituted 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol (8) scaffold. In general, compared to the corresponding 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols, compounds of type 9 were potent σ receptor ligands with low levels of subtype selectivity, while the corresponding N-methyl-8-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecanes showed reduced affinity but greater selectivity for σ2 receptors. The N-methyl-11-aminopentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecan-8-ones demonstrated the poorest σ receptor affinities, suggesting that 4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols interact with σ receptors in the bridged hemiaminal form rather than as the non-transannular, aminoketone tautomers. Several compounds of type 8, 9, and 14 were assessed for their ability to inhibit nitric oxide release in vitro, and demonstrated comparable or greater efficacy than 4-phenyl-1-(4-phenylbutyl)piperidine (PPBP), an established neuroprotective σ ligand with NOS inhibitory activity.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.TIPS.2018.11.001
Abstract: Deficits in social behavioral domains, such as interpersonal communication, emotion recognition, and empathy, are a characteristic symptom in several neuropsychiatric disorders, including schizophrenia and autism spectrum disorder (ASD). The neuropeptide oxytocin (OT) has emerged as a key regulator of erse social behaviors in vertebrates and, thus, has been identified as a potential therapeutic target for improving social dysfunction. In recent years, the field of OT research has seen an explosion of scientific inquiry, producing a more comprehensive picture of oxytocinergic signaling and the pathways that regulate its release and degradation in the brain. In this review, we provide an analysis of how this information is being exploited to accelerate the discovery of novel oxytocinergic therapeutics.
Publisher: Springer US
Date: 16-10-2021
Publisher: Elsevier BV
Date: 2012
Publisher: Wiley
Date: 28-09-2010
DOI: 10.1111/J.1471-4159.2010.06992.X
Abstract: Neurogenesis, the birth of new neurons, continues throughout adulthood in the human subventricular zone (SVZ) and hippoc us. It is not known how levels of putative proliferation-regulating factors change with age in human adult neurogenic areas. The current project employed ELISAs to investigate changes in levels of putative proliferation-regulating factors in the healthy human SVZ and dentate gyrus throughout the adult lifespan (18-104 years). Levels of brain-derived neurotrophic factor, basic fibroblast growth factor and interleukin (IL)-1β were significantly higher in the hippoc us than in the SVZ and levels of glial-derived neurotrophic factor and transforming growth factor-α were significantly higher in the SVZ (p < 0.005), suggesting that factors with predominant influences on neurogenesis differ between the two human adult neurogenic areas. Hippoc al levels of transforming growth factor-β1 strongly increased with age (n = 9, p < 0.01), whereas hippoc al and SVZ levels of brain-derived neurotrophic factor, epidermal growth factor, basic fibroblast growth factor, glial-derived neurotrophic factor, heparin-binding epidermal growth factor, insulin-like growth factor-1, IL-1β, IL-6 and transforming growth factor-α did not change significantly with age in the SVZ or hippoc us. These findings suggest regulation of the adult neurogenic environment in the human brain may differ over time from that in other species.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.EJMECH.2017.05.013
Abstract: The neuropeptide oxytocin has been implicated in multiple central nervous system functions in mammalian species. Increased levels have been reported to improve trust, alleviate symptoms related to autism and social phobias, and reduce social anxiety. Hoffman-La Roche published a patent claiming to have found potent small molecule oxytocin receptor agonists, smaller than the first non-peptide oxytocin agonist reported, WAY 267,464. We selected two of the more potent compounds from the patent and, in addition, created WAY 267,464 hybrid structures and determined their oxytocin and vasopressin receptor activity. Human embryonic kidney and Chinese hamster ovary cells were used for the expression of oxytocin or vasopressin 1a receptors and activity assessed via IP1 accumulation assays and calcium FLIPR assays. The results concluded that the reported compounds in the patent and the hybrid structures have no activity at the oxytocin or vasopressin 1a receptors.
Publisher: Elsevier BV
Date: 03-2018
Publisher: The Japan Institute of Heterocyclic Chemistry
Date: 2016
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.EJPS.2016.09.026
Abstract: The 18kDa translocator protein (TSPO) is a target for novel glioblastoma therapies due to its upregulation in this cancer and relatively low levels of expression in the healthy cortex. The pyrazolo[1,5-a]pyrimidine acetamides, exemplified by DPA-713 and DPA-714, are a class of high affinity TSPO ligands with selectivity over the central benzodiazepine receptor. In this study we have explored the potential anti-glioblastoma activity of a library of DPA-713 and DPA-714 analogues, and investigated the effect of amending the alkyl ether chain on TSPO affinity and functional potential. All ligands demonstrated nanomolar affinity for TSPO, but showed erse functional activity, for ex le DPA-713 and DPA-714 did not affect the proliferation or viability of human T98G glioblastoma cells, while the hexyl ether and benzyl ether derivatives decreased proliferation of T98G cells without affecting proliferation in human fetal glial SVGp12 cells. These ligands also induced apoptosis and dissipated T98G mitochondrial membrane potential. This suggests that the nature of the alkyl ether chain of pyrazolo[1,5-a]pyrimidine acetamides has little influence on TSPO affinity but is important for functional activity of this class of TSPO ligands.
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 07-06-2006
Abstract: The propagation of Ca2+ waves in a network of microglial cells, after its initiation by glutamate, is mediated by purinergic transmission. In this study, we investigated the mechanisms by which glutamate releases ATP from cultured spinal cord microglia. The 4-fold increase in ATP release from microglia in response to glutamate (0.5 mM) was blocked by alpha-aminohydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptor antagonist 6-cyano-7-nitroguinoxaline-2,3-dione and specific AMPA receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) but not by N-methyl-d-aspartic acid or metabotropic glutamate receptor antagonists. Glutamate acting on AMPA receptors evoked an ATP release that was blocked by antagonizing the rise in intracellular Ca2+ as a result of its release from internal stores as well as by antagonizing protein kinase C with chelerythrine. Glutamate-stimulated ATP release was significantly antagonized by the cystic fibrosis transmembrane conductance regulator (CFTR) blockers flufenamic acid and glibenclamide. A role for the CFTR was further confirmed using microglia from CFTR knockout mice, which released significantly less ATP than microglia from control wild-type mice in response to glutamate. Use of 6-methoxy-1-(3-sulfopropyl)quinolinium fluorescence assay revealed functional CFTR in microglia. These observations suggest that glutamate acted on microglial AMPA receptors to stimulate release of Ca2+ from intracellular stores as well as a Ca2+-dependent isoform of protein kinase C, which then acts to trigger release of ATP with the CFTR acting as a regulator of the ATP release process, perhaps through another channel or transporter.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6MD00523C
Abstract: The 18 kDa translocator protein (TSPO) is a target for development of diagnostic imaging agents for glioblastoma and neuroinflammation.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.EJMECH.2017.10.059
Abstract: WAY-267,464 (1) and twelve conformationally rigid analogues (3a-f-4a-f) were synthesised, characterised and evaluated in cellular assays with the aim of systematically exploring interactions with the oxytocin receptor (OTR). Each analogue was evaluated in radioligand binding displacement assays at both human OTR and arginine vasopressin 1a receptors (V
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.NEUROSCIENCE.2010.10.080
Abstract: Interleukin-10 (IL-10) is a cytokine with important endogenous and therapeutic anti-inflammatory effects. Given this, it is of interest to investigate factors that modulate IL-10 levels in the central nervous system. IL-10 is released after lipopolysaccharide (LPS) stimulation of microglia. Microglia also express functional glutamate receptors and in inflammatory conditions are exposed to increased levels of glutamate. The aim of this research, then, is to investigate whether glutamate can modulate lipopolysaccharide stimulation of IL-10 release from neonatal rat spinal cord microglia. Enzyme-linked immunosorbent assays (ELISAs) were used to quantify IL-10 release from cultured neonatal spinal cord microglia and reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure IL-10 mRNA expression. Glutamate (1 mM) significantly increased LPS (1 μg/ml)-stimulated IL-10 release from microglia by 172% (EC(50) of 103 μM) and significantly upregulated IL-10 mRNA levels. Glutamate potentiated LPS-stimulated IL-10 release by binding all subtypes of glutamate receptor. These results show that glutamate substantially increases the release of an anti-inflammatory cytokine from neonatal spinal cord microglia activated by a high concentration of LPS.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.EJMECH.2015.11.050
Abstract: A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition radioligand binding assays at human oxytocin (OT) and arginine vasopressin 1a (V1a) receptors. Physiological activity was determined using whole cell IP1 accumulation assays. Under these conditions, WAY-267,464 had higher affinity for the V1a receptor compared to the OT receptor (8.5x more selective) with poor functional selectivity (2x selective for OT receptor agonism over V1a receptor antagonism). Methylation of the resorcinol moiety (3) reversed the OT receptor pharmacological profile, removing agonist activity and inducing antagonist activity, without altering V1a receptor pharmacology. All flexible tethered derivatives removed OT receptor affinity and activity resulting in the generation of highly selective V1a receptor ligands.
Publisher: Wiley
Date: 08-08-2006
DOI: 10.1111/J.1471-4159.2006.04133.X
Abstract: ATP has recently emerged as a key molecule mediating pathological pain. The aim of this study was to examine whether spinal cord astrocytes could be a source of ATP in response to the nociceptive neurotransmitters glutamate and substance P. Glutamate stimulated ATP release from these astrocytes and this release was greatly potentiated by substance P, even though substance P alone did not elicit ATP release. Substance P also potentiated glutamate-induced inward currents, but did not cause such currents alone. When glutamate was applied alone it acted exclusively through alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptors to stimulate Ca(2+) influx-dependent ATP release. However, when substance P was co-applied with glutamate, ATP release could be elicited by activation of NMDA and metabotropic glutamate receptors. Activation of neurokinin receptor subtypes, protein kinase C and phospholipases A(2), C and D were needed for substance P to bring about its effects. These results suggest that astrocytes may be a major source of ATP in the spinal cord on activation of nerve fibres that release substance P and glutamate.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9OB00656G
Abstract: New 18 F-fluorinated benzimidazole 5-sulfones with low nanomolar binding affinity were synthesised as PET-radioligand candidates for the CB2 receptor.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.BMCL.2017.04.005
Abstract: We report on P2X
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.NEUROSCIENCE.2012.01.039
Abstract: Interleukin-10 (IL-10) has important anti-inflammatory effects and can be protective in inflammatory conditions, such as chronic pain and infection. Exploring factors that modulate IL-10 levels may provide insight into pathomechanisms of inflammatory conditions and may provide a method of neuroprotection during these conditions. Lipopolysaccharide (LPS) stimulation of astrocytes is a source of IL-10 hence, it is of interest to investigate factors that modulate this process. Glutamate is present in increased concentrations in inflammatory conditions, and astrocytes also express glutamate receptors. The present study, therefore, investigated whether glutamate modulates LPS stimulation of IL-10 release from neonatal spinal cord astrocytes. Enzyme-linked immunosorbent assays (ELISAs) were used to quantify IL-10 release from cultured neonatal spinal cord astrocytes, and reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure IL-10 mRNA expression. Glutamate (1 mM) significantly increased LPS (1 μg/ml)-stimulated IL-10 release from astrocytes by 166% and significantly upregulated IL-10 mRNA levels. Glutamate synergistically signaled through metabotropic glutamate receptor subgroups and the phospholipase C signaling pathway. Spinal cord astrocytes may, therefore, play a larger anti-inflammatory role than first thought in situations where glutamate and a high concentration of Toll-like receptor 4 (TLR4) agonists are present.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1MD00065A
Abstract: Indole-2-carboxamides: antitumour potential and selectivity against paediatric glioma.
Publisher: American Chemical Society (ACS)
Date: 16-08-2019
DOI: 10.1021/ACS.JMEDCHEM.9B00980
Abstract: Development of neuroinflammation agents targeting the translocator protein (TSPO) has been hindered by a common single nucleotide polymorphism (A147T) at which TSPO ligands commonly lose affinity. To this end, carbazole acetamide scaffolds were synthesized and structure activity relationships elaborated to explore the requirements for high-affinity binding to both TSPO wild type (WT) and the polymorphic TSPO A147T. This study reports high binding affinity and nondiscriminating TSPO ligands.
Publisher: MDPI AG
Date: 25-11-2022
Abstract: The use of cellular models is a common means to investigate the potency of therapeutics in pre-clinical drug discovery. However, there is currently no consensus on which model most accurately replicates key aspects of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) pathology, such as accumulation of insoluble, cytoplasmic transactive response DNA-binding protein (TDP-43) and the formation of insoluble stress granules. Given this, we characterised two TDP-43 proteinopathy cellular models that were based on different aetiologies of disease. The first was a sodium arsenite-induced chronic oxidative stress model and the second expressed a disease-relevant TDP-43 mutation (TDP-43 M337V). The sodium arsenite model displayed most aspects of TDP-43, stress granule and ubiquitin pathology seen in human ALS/FTD donor tissue, whereas the mutant cell line only modelled some aspects. When these two cellular models were exposed to small molecule chemical probes, different effects were observed across the two models. For ex le, a previously disclosed sulfonamide compound decreased cytoplasmic TDP-43 and increased soluble levels of stress granule marker TIA-1 in the cellular stress model without impacting these levels in the mutant cell line. This study highlights the challenges of using cellular models in lead development during drug discovery for ALS and FTD and reinforces the need to perform assessments of novel therapeutics across a variety of cell lines and aetiological models.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2003
DOI: 10.1097/00001756-200312020-00009
Abstract: The mechanisms involved in autocrine ATP release from cultured astrocytes isolated from the rat cortex were investigated using an online bioluminescence technique. Astrocytes released ATP in response to application of 10 microM uridine triphosphate, which was blocked by the non-specific purinergic receptor antagonist suramin. Intracellular pathways of the uridine triphosphate-stimulated ATP release were seen to involve inositol triphosphate and calcium with the assistance of the Golgi-complex and cytoskeleton as the release was inhibited by phospholipase C antagonist lithium, endoplasmic reticulum calcium-dependent ATPase inhibitor thapsigargin, F-actin interruptor cytochalasin D and Golgi-complex interruptor brefeldin A. The uridine triphosphate-stimulated ATP release was also potently blocked by exocytosis inhibitor botulinum toxin A and anion transporter blockers furosemide and glibenclamide. These results suggest that calcium-dependent exocytosis and transportation via anion transporters are the predominant secretion mechanisms for uridine triphosphate-stimulated ATP release from cortical astrocytes.
Publisher: American Chemical Society (ACS)
Date: 21-12-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9MD00580C
Abstract: A loss in binding affinity at A147T relative to WT TSPO is seen with most TSPO ligands. Provision of hydrogen-bonding opportunities on indole carboxamides rescues this loss in affinity.
Publisher: Wiley
Date: 2005
DOI: 10.1111/J.1460-9568.2004.03831.X
Abstract: The mechanisms by which uridine triphosphate (UTP) stimulates ATP release from Schwann cells cultured from the sciatic nerve were investigated using online bioluminescence techniques. UTP, a P2Y(2) and P2Y(4) receptor agonist, stimulated ATP release from Schwann cells in a dose-dependent manner with an ED(50) of 0.24 microm. UTP-stimulated ATP release occurs through P2Y(2) receptors as it was blocked by suramin which inhibits P2Y(2) but not P2Y(4) receptors. Furthermore, positive immunostaining of P2Y(2) receptors on Schwann cells was revealed and GTP, an equipotent agonist with UTP at rat P2Y(4) receptors, did not significantly stimulate ATP release. UTP-stimulated ATP release involved second messenger pathways as it was attenuated by the phospholipase C inhibitor U73122, the protein kinase C inhibitor chelerytherine chloride, the IP(3) formation inhibitor lithium chloride, the cell membrane-permeable Ca(2+) chelator BAPTA-AM and the endoplasmic reticulum Ca(2+)-dependent ATPase inhibitor thapsigargin. Evidence that ATP may be stored in vesicles that must be transported to the cell membrane for exocytosis was found as release was significantly reduced by the Golgi-complex inhibitor brefeldin A, microtubule disruption with nocodazole, F-actin disruption with cytochalasin D and the specific exocytosis inhibitor botulinum toxin A. ATP release from Schwann cells also involves anion transport as it was significantly reduced by cystic fibrosis transmembrane conductance regulator inhibitor glibencamide and anion transporter inhibitor furosemide. We suggest that UTP-stimulated ATP release is mediated by activation of P2Y(2) receptors that initiate an IP(3)-Ca(2+) cascade and protein kinase C which promote exocytosis of ATP from vesicles as well as anion transport of ATP across the cell membrane.
Publisher: American Chemical Society (ACS)
Date: 25-08-2017
DOI: 10.1021/ACSCHEMNEURO.7B00272
Abstract: Adamantanyl benzamide 1 was identified as a potent P2X
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.EJPHAR.2021.174667
Abstract: Antagonists of the P2X7 receptor (P2X7R) have the potential to treat diseases where neuroinflammation is present such as depression, chronic pain and Alzheimer's disease. We recently developed a structural hybrid (C1 1-((adamantan-1-yl)methyl)-2-cyano-3-(quinolin-5-yl)guanidine) of a purported competitive P2X7R antagonist (C2 2-cyano-1-((1S)-1-phenylethyl)-3-(quinolin-5-yl)guanidine) and a likely negative allosteric modulator (NAM) of the P2X7R (C3 N-((adamantan-1-yl)methyl)-2-chloro-5-methoxybenzamide). Here we aimed to pharmacologically characterize C1, to gain insights into how select structural components impact antagonist interaction with the P2X7R. A second aim was to examine the role of the peptide LL-37, an apparent activator of the P2X7R, and compare the ability of multiple P2X7R antagonists to block its effects. Compounds 1, 2 and 3 were characterised using washout, Schild and receptor protection studies, all using dye uptake assays in HEK293 cells expressing the P2X7R. LL-37 was examined in the same HEK293 cells and THP-1 monocytes. Compounds 2 and 3 acted as a BzATP-competitive antagonist and NAM of the P2X7R respectively. Compound 1 was a slowly reversible NAM of the P2X7R suggesting the incorporation of an appropriately positioned adamantane promotes binding to the allosteric site of the P2X7R. LL-37 was shown to potentiate the ability of ATP to induce dye uptake at low concentrations (1-3 μg mL
Publisher: American Chemical Society (ACS)
Date: 23-10-2015
DOI: 10.1021/ACS.JMEDCHEM.5B01288
Abstract: We show that changing the number and position of nitrogen atoms in the heteroatomic core of a pyrazolopyrimidine acetamide is sufficient to induce complex binding to wild type human TSPO. Only compounds with this complex binding profile lacked intrinsic effect on glioblastoma proliferation but positively modulated the antiproliferative effects of a synthetic TSPO ligand. To the best of our knowledge this is the first demonstration of allosteric-like interaction at the wild type human TSPO.
Publisher: Springer Berlin Heidelberg
Date: 09-11-2013
Publisher: MDPI AG
Date: 28-06-2019
DOI: 10.3390/IJMS20133161
Abstract: Neuroinflammation is an inflammatory response in the brain and spinal cord, which can involve the activation of microglia and astrocytes. It is a common feature of many central nervous system disorders, including a range of neurodegenerative disorders. An overlap between activated microglia, pro-inflammatory cytokines and translocator protein (TSPO) ligand binding was shown in early animal studies of neurodegeneration. These findings have been translated in clinical studies, where increases in TSPO positron emission tomography (PET) signal occur in disease-relevant areas across a broad spectrum of neurodegenerative diseases. While this supports the use of TSPO PET as a biomarker to monitor response in clinical trials of novel neurodegenerative therapeutics, the clinical utility of current TSPO PET radioligands has been h ered by the lack of high affinity binding to a prevalent form of polymorphic TSPO (A147T) compared to wild type TSPO. This review details recent developments in exploration of ligand-sensitivity to A147T TSPO that have yielded ligands with improved clinical utility. In addition to developing a non-discriminating TSPO ligand, the final frontier of TSPO biomarker research requires developing an understanding of the cellular and functional interpretation of the TSPO PET signal. Recent insights resulting from single cell analysis of microglial phenotypes are reviewed.
Publisher: Springer Science and Business Media LLC
Date: 19-07-2019
DOI: 10.1038/S41582-019-0231-Z
Abstract: Frontotemporal dementia (FTD) refers to a group of progressive neurodegenerative disorders with different pathological signatures, genetic variability and complex disease mechanisms, for which no effective treatments exist. Despite advances in understanding the underlying pathology of FTD, sensitive and specific fluid biomarkers for this disease are lacking. As in other types of dementia, mounting evidence suggests that neuroinflammation is involved in the progression of FTD, including cortical inflammation, microglial activation, astrogliosis and differential expression of inflammation-related proteins in the periphery. Furthermore, an overlap between FTD and autoimmune disease has been identified. The most substantial evidence, however, comes from genetic studies, and several FTD-related genes are also implicated in neuroinflammation. This Review discusses specific evidence of neuroinflammatory mechanisms in FTD and describes how advances in our understanding of these mechanisms, in FTD as well as in other neurodegenerative diseases, might facilitate the development and implementation of diagnostic tools and disease-modifying treatments for FTD.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.EJMECH.2017.02.060
Abstract: Here we report adamantyl cyanoguanidine compounds based on hybrids of the adamantyl amide scaffold reported by AstraZeneca and cyanoguanidine scaffold reported by Abbott Laboratories. Compound 27 displayed five-fold greater inhibitory potency than the lead compound 2 in both pore-formation and interleukin-1β release assays, while 35-treated mice displayed an antidepressant phenotype in behavioral studies. This SAR study provides a proof of concept for hybrid compounds, which will help in the further development of P2X
Publisher: Wiley
Date: 17-10-2018
Abstract: Novel boron-rich, carboranyl-indole carboxamide ligands were prepared and found to effectively target the 18 kDa translocator protein (TSPO), an upregulated mitochondrial membrane-bound protein which has been observed in variety of tumor cell lines and its expression appears to be proportional to the degree of tumorigenicity, emphasizing a key role in cancer cell proliferation. Both boronated compounds displayed remarkably high affinities for the TSPO. In addition, the in vitro uptake of these compounds into T98G human glioma cells was found to be 25- to 100-fold greater than that of clinical boron neutron capture therapy (BNCT) agents.
No related organisations have been discovered for Eryn Werry.
Start Date: 02-2024
End Date: 01-2027
Amount: $723,641.00
Funder: Australian Research Council
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